Safety study of trifarotene cream in lamellar ichthyosis
Research type
Research Study
Full title
A Phase 2 Randomized, Multi-center, Double-blind, Vehicle-controlled, 12-Week, Safety, Efficacy, and Systemic Exposure Study followed by a 12-Week Open-label Extension of Trifarotene (CD5789) Cream HE1 in Adults and Adolescents with Autosomal Recessive Ichthyosis with Lamellar Scale
IRAS ID
249647
Contact name
Edel O'Toole
Contact email
Sponsor organisation
Mayne Pharma
Eudract number
2018-003272-12
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
NCT Number, NCT03738800
Duration of Study in the UK
1 years, 12 months, 30 days
Research summary
Summary of Research
Lamellar ichthyosis (LI) is recognised as a severe form of ichthyosis that persists throughout life.While usually not life threatening, LI can result in disability, partial deafness, poor adaptation to environmental conditions (due to hypohdrosis (decreased sweating)), severe discomfort (pruritus (itching)), fissuring of the skin and significant psychosocial impact.
Although the primary objective of this study is safety in the patient population with LI, the potential benefits of study participation is that patients with LI may experience a reduction in their LI symptoms as a result of treatment with trifarotene (CD5789) cream.
LI has significant unmet medical need for safer and more effective therapies.
The study compares the safety, efficacy of two concentrations of trifarotene cream 100 µg/g or 200 µg/g patients with moderate to severe lamellar ichthyosis (LI) to 12 weeks. All patients are treated twice weekly.
Fifteen Adults will be recruited initially and after 28 Days of treatment all data will be reviewed if no issues are identified then the study will be extended to included patients between ages 12 and 17 years.
It is recommended that only 1 household member will be included in the study.The maximum study duration for each Patient is approximately 140 days (20 weeks).
Screening - Washout: Up to 35 days during which patients must stop using prohibited topical and systemic treatments.Patients choose 2 specific days per week at least 3 days apart to apply the IP.
Patients should not shower, bathe, or swim for at least 4 hours after the IP application.A local tolerability assessment scale will be completed at each clinic visit.
Patients will have assessment on scaling, roughness, fissuring, patient palms and soles, including analysis of Blood and Urine, blood pressure and pulse, height, weight, BMI and ECG to ensure that patients can be included in the study.Summary of Results
Researchers look at the results of many studies to decide which drugs work best and are safest for patients. It takes many participants and many studies all around the world to advance medical science.
This study was a phase 2 study. A phase 2 study looks at how well the study drug works in a specific disease and how safe it is. Another important goal for phase 2 studies is to find out how much and how often the study drug should be used or taken. Phase 2 studies sometimes compare the study drug with a “placebo”, which seems the same as the study drug, but has no active ingredient. In phase 2 studies, patients are normally assigned to a treatment group by chance (randomly selected).
This summary only shows the results from this particular study (referenced in the title).1. General Information About the Clinical Study
1.1 Where Was the Study Done?
This study took place in the following countries:
European Union (EU):
• France
• Germany
• Spain
Rest of World:
• Australia
• Canada
• Israel
• Ukraine
• United Kingdom
• United States.
1.2 When Was the Study Done?
This study started in June 2019 and ended in July 2021. The sponsor decided to close the study early because the main objectives of the study could not be met.
1.3 What Were the Main Objectives of This Study?
In this study, researchers tried to find out whether a new study drug, Trifarotene (CD5789) Cream HE1 (referred to as Trifarotene Cream throughout the remainder of this text), could help patients with a rare genetic condition called lamellar ichthyosis. This condition affects the skin from birth and throughout an individual’s whole life and causes scaling over the whole of the body. Lamellar ichthyosis is one of a number of different types of ichthyosis, and this study only looked at patients with lamellar ichthyosis. Researchers also looked at whether this study drug was safe.
The study drug was compared with a placebo. This comparison was done to see whether any improvements to the skin condition or side effects were caused by the study drug or a “placebo effect” (this is where some people believe they experience an effect after receiving a treatment that has no known medical effect). This also allowed researchers to see whether any benefit of the study drug outweighed any possible side effects. In this study, the placebo was a “vehicle” cream, which means the cream without the active ingredient.
Study results were checked part way through the study to assess whether the study was going to meet the main objective. The study was stopped early because the main objective was not going to be reached.2. What Patients Were Included in This Study?
2.1 The Number of Patients Included in the Study
About a total of 120 patients with moderate to severe lamellar ichthyosis were planned to take part in the study. As the study was closed early, only 65 patients who had moderate to severe lamellar ichthyosis took part.
The study was performed in 26 patients in the EU (13 in France, 8 in Germany, and 5 in Spain) and in 39 patients in the Rest of World (4 in Australia, 3 in Canada, 3 in Israel, 11 in Ukraine, 1 in the United Kingdom, and 17 in the United States).
2.2 Age Group and Gender Breakdown
The majority of patients in this study were adults (aged 18 years or over) and the rest were adolescents (aged 12 through 17 years). The youngest patient was aged 12 years and the oldest was aged 76 years. The average age of patients in this study was 33 years.
Overall, there were 41 females and 24 males in the study, of which 20 females and 6 males were in EU countries.
2.3 Inclusion and Exclusion Criteria
To take part in this study, patients must have been diagnosed with moderate to severe lamellar ichthyosis.
To start with, patients aged 18 years or over were recruited into this study. Once the study drug was determined to be safe in these patients, the study was also opened up to patients aged 12 through 17 years.
Both males and females could take part in the study. In patients who could have children, effective birth control methods had to be used throughout the study and for 1 month after the last application of study drug. Pregnant or breastfeeding patients were not allowed to take part in the study.
Patients were excluded from the study if they had:
• Any skin infection, or any stinging or burning, or any type of ichthyosis apart from lamellar ichthyosis
• Previously been treated with the study drug, were allergic to any ingredient in the study drug, or if they had any other medical history that may put them at risk in the study
• Certain abnormal laboratory results at Screening
• Sensitivity to sunlight, or had been exposed to excessive ultraviolet light (e.g., sunbathing or phototherapy) within 1 month before the first application of the study drug, or was planning it during the study3. Which Medicines Were Used?
Patients aged 18 years or over with lamellar ichthyosis were put into 3 treatment groups by chance (randomised) to make the study fair. The first part of this study was “double blinded”, which means that neither patients nor doctors knew who was given which treatment. This was done to make sure that the study results were not influenced in any way. The patients were either given Trifarotene Cream at a dose of 100 µg/g or 200 µg/g, or a placebo known as “vehicle” cream. The “vehicle” cream had the same appearance as the study drug but had no active ingredient. Patients applied the cream twice a week for 90 days to the affected skin areas.
After 22 patients completed 28 days of treatment, the study was also opened up to patients aged 12 through 17 years. These patients were put into groups in the same way as above. Patients applied the cream twice a week for 90 days.
All patients who completed the 90-day, double-blinded part of the study were then eligible and had the option to take part in the second part of the study, where all patients were given Trifarotene Cream at a dose of 200 µg/g, twice a week, for 90 days. Both the patients and doctors knew what treatment was being given. This is known as “open label”.4. What Were the Side Effects?
Adverse reactions, also known as side effects, are unwanted medical events (e.g., headache) that may happen during the study after receiving the study treatment. Not all the patients in this study had side effects.
There were no deaths, serious side effects or severe treatment-related side effects in any of the treatment groups in either the double-blinded or open-label part of the study. No patient was withdrawn from the study because of a side effect.
The most common side effects during the double-blinded part of the study were related to the skin, with itchy skin (pruritus), raised spots on the skin (papule), itchy, dried, cracked, and blistered skin (dermatitis), and eczema being the most common. Pruritus, papule, and dermatitis were each experienced by 1 out of 44 patients (2.3%) who used Trifarotene Cream. Eczema was experienced by 1 out of 21 patients (4.8%) who used “vehicle” cream.
In the open-label part of the study, the most common side effects were also related to the skin, with skin pain, rash, cracks in the skin due to intense dryness and thickened skin (fissures), and skin irritation being the most common.
Most patients throughout the study did not report any redness, stinging, burning, or itching where the treatment was applied.5. What Were the Overall Results of the Study?
During the double-blind part of the study, patients were either given Trifarotene Cream at a dose of 100 µg/g or 200 µg/g, or “vehicle” cream. Patients applied the cream twice a week for 90 days. Everyone was followed to test whether their lamellar ichthyosis improved, stayed the same, or got worse.
All patients who completed the 90-day, double-blinded part of the study were then eligible to take part in the second part of the study, where all patients were given Trifarotene Cream at a dose of 200 µg/g, twice a week, for 90 days. Patients were also assessed to see whether their lamellar ichthyosis had improved.
To achieve the main goal of the study, 70% of patients who received Trifarotene Cream had to show a specified improvement in the symptoms of their lamellar ichthyosis during the double blind part of the study. When study results for all patients were checked part way through the study, only 2 out of 48 patients (4%) had seen the required improvement in their treated skin areas. Of the 32 patients who were given Trifarotene Cream for 90 days, 2 out of 32 patients (6.3%) saw the required improvement in their treated skin areas. Due to the low treatment success observed in the double blinded part of the study, it was concluded that the main goal of the study would not be met if more patients were enrolled.
No safety concerns were seen during this study and treatments were generally well tolerated.6. How Has This Study Helped Patients and Researchers?
As the study was stopped early because the main objective was not going be reached, the results of this study should be interpreted with caution.7. Are There Plans for Further Studies?
These results need to be thoroughly analysed and discussed with the appropriate experts and regulators before deciding whether any further studies will be conducted.8. Where Can I Find Out More Information About This Study?
To learn more about this study, you can look up the official study title or go to:
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London - West London & GTAC Research Ethics Committee
REC reference
19/LO/0581
Date of REC Opinion
14 Oct 2019
REC opinion
Further Information Favourable Opinion